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Electroencephalographic studies of the encephalopathies:
ELECTROENCEPHALOGRAPHIC
STUDIES OF T H E
ENCEPHALOPATHIES : II. SERIAL STUDIES IN TUBERCULOUS MENINGITIS WILMA SHAW, R.N., RICHARD P. SCHMIDT,M.D., LEwis L. LEvy, M.D. a n d EPHRAIM ROSEMAN, M.D. Sections of Neurology and Electroencephalography, University of Louisville, School of Medicine, and the Louisville General Hospital, Louisville, Ky.
RICHARD C.
TURRELL,M.D.,
This report covers a 41/~ year period during which serial electroencephalographic and clinical correlations were made in 57 proven eases of tuberculous meningitis. The purpose of this paper is to point out the value of serial electroencephalograms in the diagnosis and prognosis of this disease. METHODS Electroencephalograms were performed as soon as possible after admission to the hospital on patients suspected of having tuberculous meningitis. Thereafter tracings were taken at weekly intervals or more frequently if clinical change occurred. In each instance close clinical supervision and electroencephalographic correlation was made by one of the authors. EEGs were made on a Grass eight-channel ink writing oscillograph. A minimum of 13, 27 gauge, needle electrodes were inserted into the scalp and ear lobes, using bipolar as well as monopolar leads (with an average reference or one on both ears or on the cortex). MATERIAL Ages: There were 36 children and 21 adults. The ages ranged from 4 months to 74 years. Thirty-two patients were less than 7 years old. Seven were between 7 and 20 years; 18 were in the 21 to 74 year range. Sex and races: Of the females. 18 were white and 8 were negro. Twenty males were white and 11 were negro. Diagnostic criteria: All cases had a predominantly lymphocytic meningitis with a decreased cerebro-spinal fluid (CSF) sugar and chlorides. In 48 the tubercle bacillus was isolated from the CSF by direct smear,
culture, guinea pig inoculation or were found in the tissues at post mortem examination. In the remaining 9 the diagnosis was suspected by at least 2 characteristic CSF examinations plus evidence of extra central nervous system (CNS) tuberculosis. The characteristic spinal fluid contained up to 500 cells (predominantly lymphocytes) per mm s, sugar less than 30 rag. per cent, chlorides less than 600 mg. per cent and an elevated total protein. Tuberculosis outside the CNS: Only 7 subjects showed no evidence of extra-CNS tuberculosis. Six of these were children and one was an adolescent. The remainder had pulmonary, miliary, bone or other visceral evidence of the disease. Duration of life: The duration of life in those that died ranged from 3 to 360 days (av. 88 days). Eleven patients are living at present (19 per cent survival rate}. Only one adult in the series is alive. He is under treatment and doing well after 279 days of streptomycin therapy. The remaining 10 are children who have lived from 200 to 1640 days. They are all clinically well. Three are still receiving streptomycin. Three others have been followed 4 years or longer. Complications: As noted in table I there was a high incidence of neurological complications. The most frequent were hemiparesis and subarachnoid block with secondary hydrocephalus. Seizures: Forty-seven patients (82 per cent) had seizures at some time during their illness. The majority of these were of a convulsive nature. A few developed ps:...,homotor seizures.
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.54
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1 2 3 4 .i 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 2.7 24 2.5 26 27
28 29 3n 31 30 i.7 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57
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W. SHAW.
Age
in years
1 1
4/l!? 5/12 i/12 8112 S/l” 11/l” 11/12 11/12 l/12
1 l/12 1 3/12
1 5/12 1 6/12 1 10/12 1 IO/l2 2 2 2 2 2 6/12 2 6/l” 2 (1/l? 3 3 3 c/12 4 5 6 6 6 (i 1: 11 14 I6 18 10 OR 24 24 24 26 28 31 31 33 33 34 36 39 44 45 45 49 74
R. P. SCHMIDT,
L. I,. LEVY
awl E. ROSEMAN
Sex avd Race (1)
HOW prorcx (2)
Extra Cns Tbc (3
CM WF C’M WM CM WM WM WM WM WM WF WF WF t:;M WF WM war WF CF WM WF x.31 WF WF WM WF WM wxr WF CF W’bl WM CM (‘F WM WF CF WF WF CM WF CF CM CM WF CF WM CF WM WF CM WM WF WM CM (‘F CM
S;C F C S:G G:P F s G :t: s r C F F P S;C S C G C S;C;P F F G;S s F S:C;G s S s s F G P 8:P S;P S:(’ S P;G S C P s ;c P C;G
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None
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I&/s of Life (4) e____ 330 I32
18 i8 35 “I) _I Ii0 16 209 L 37 (ii 2.52 106
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* IM Streptnmyein ody. ** Untreated. (1) C-Negro; W-Crucasian. (2) S-Smear; C-Culture; P-Post Mortem : G-Guinea Pig: F-Presumptive. (3) M-Miliary ; P-Pulmounry ; B-Bone ; 8.Selpingitin; E-Epididymitis; Pe-Peritonitis: R-Renal. (4) Computed ZIR of 1 July JO:
I,
E E G S T U D I E S OF T H E E N C E P H A L O P A T H I E S
55
TABLE I A S U M M A R Y O F 57 C A S E S O F T U B E R C U L O U S M E N I N G I T I S "
Seizures X X X X X X X X X X X X X X X X X X O X O X X X O X X O X X X X X X X X X X X X O X 0 0 X O X X O X X O X X X X X
Number of E g g ' s 38 3 4 3 5 1 10 2 11 5 5 II 3 1 16 4 2 5 1 2 14 7 5 1 6 15 2 17 9 8 2 31 31 4 20 17 34 7 (; 4 2 19 1 3 9 2 3 5 3 7 6 5 3 28 14 4 4
Days ill prior to 12 26 4 15 5 21 14 7 5 2I 17 23 25 6 8 16 5 7 2 62 14 31 9 °7 10 21 7 11 15 12 90 49 7 3 8 15 7 22 12 64 30 30 14 12 6 5 17 12 29 6 20 1 7 12 39 14 4
Initial EEG Days R x prior to 0 16 1 4 0 4 4 0 0 0 2 1 25 0 7 10 1 o 3 6O 0 ]~ o 16 .5 TO 0 4 0 .q 80 42 1 1 0 1 2 0 0 56 86 0 o o 0 0 0 0 18 6 11 0 0 0 14 0 0
Average frequency 3 2.5 1 2.5 2 .5 2.5 2 2.5 2 2 1 1.5 3.5 4 2 1.5 2.5 1 3.5 1.5 .5 4.5 1 2.5 2.5 l 2 1.5 1 1 5 1.5 1.5 2..5 1.5 5 8 3 9 7 2 9 2.5 6 7 7 9.5 7 9 10 7 7 7 2.5 15 3.5
R~marlcs (5) Subd. llygrom't; hydro. Hydro. L. L. L. R.
Hemip. Hemip. Hemip. Hemip.
L. H e m i p . ; Subaraeh. block. Men. folh)wed Rx for exl-a C N S tbe. Decerebrate; hydro. Deeerebrate R. Hemip. Deaf Decerebrate ; hydro. R. Hemip. R. Hemip. Hydro. R. H e m i p . ; Improved. Hydro. Measles prior to men. L. Hemip. Well WeU Measles prior to men. ; R Hcmip. Cerebral m u m p s d u r i n g illness ; Des: Subarach. block ; L e f t Ilemip. Hydra. Decerebrate Cerebral m u m p s d u r i n g i Ihmss. Subarach. block Measles prior to men. Blind ; quadriplegia S M N eneeph.; d e a f ; L. Hemip. Quadriparetic ; now wel! Men. 2 days post p a r t u m P a r a p l e g i c ; subaraeh. Idoek Men. developed under S M N Rx Hydro.; L. Ile/nip. R. Hemip.
Tubereuloma R. Cerebellum Men. followed Rx for ext ra-CNS tbe. L. Hemip. R. Hemip. Men. post p a r t u m L. Hemip. Men. followed Rx for ext ra-CNS tl)e. R. Hemip. Subarach. block; now a s y m p t o m a t i c Men. followed ]~x f o r extra-CNS the. Tubereuloma R. cerebellum
L-lAving. (5) S u b d . - S u d u r a l ; H y d r o . - H y d r o e e p h a l u s ; S u b a r a c h . - S u b a r a c h n o i d ; Men.-Meningitis: S M N - S t r e p t o m y c i n ; E n c e p h . - E n e e p h a l o p a t h y ; Hemip.-Hemiparesis.
56
R. C. TURRELL,
Case A
Case
C
Case
D
W. SHAW,
R. P. SCHMIDT,
FIGURE I
L. L. LEVY
and E. ROSEMAN
Case E
Case G
EEG STUDIES OF THE ENCEPHALOPATHIES Electroencephalograms: A total of 502 E E G were performed. The average number p e r patient was 8 and ranged from one to 33. Improvement, if it occurred, was noted both clinically and electroencephalographically between the 7th and 14th day. Twentysix patients had no treatment prior to their initial E E G . An additional 17 patients had been treated for 7 days or less prior to their first record. This made a total of 43 on whom initial E E G s were performed before t h e r a p y could alter their clinical or electroencephalographic course. The remaining 14 patients had been treated for variable periods of time prior to their first E E G . Three of the latter developed meningitis during or following streptomycin t h e r a p y for extra-CNS tuberculosis. The initial E E G s of all patients were classified according to their average dominant frequency. I n children this r a n g e d from 0.5 to 4.5 c/see, with an average of 1.5. F o r adults this was much faster and a v e r a g e d 6.5 c/see. RESULTS The initial E E G s in adults and children differed markedly. In adults not treated with streptomycin the first E E G was only mildly slow. In children, however, the original record was invariably diffusely slow. This disseminated delta activity was seen in
57
children of all ages and was present irrespective of the length of illness prior to the first record. F i g u r e 1 is a compariso~ of the initial E E G s in 4 adults and 4 children with tuberculous meningitis. The adults had been ill a comparable or longer peri()d of time than the children. Electroencephalographic changes paralleled and f r e q u e n t l y preceded the clinical changes. Improvement in the clinical status was reflected in the E E G by a decrease in slow activity; clinical worsening by an increase. In adults the serial E E G changes were much less marked than in children. F i g u r e 2 contrasts the electroencephalo: graphic course of an adult and a child with tuberculous meningitis. Both received i n t r a t h e c a l and intramuscular streptomycin after recording the initial EEGs. In each instance the duration of life was short. Ca.~e A is that of a 13 months old white male who lived 37 days after the onset of tuberc~llous meningitis. Serial E E G s show progressive increase of delta activity until death. H i s clinical course was one of increasing lack o f awareness progressing to coma ~nd death. Case B is a 33 year old colored female who lived 31 days. Serial tracings show only a mild degree of slowing even just prior to death. Length of life, level of consciousness and t h e r a p y in these two cases were v e r y
Fig. 1 The initial EEG in adults and children with tuberculous meningitis. A, Seven month old negro male who developed meningeal symptoms 4 days previously. He was irritable, had a stiff neck" and a right lower facial weakness. He had received one dose of streptomycin at this time. B, Two year old white male who had a stiff neck, lethargy and no focal neurological signs at the time of this tracing. Meningeal symptoms began 5 days earlier. He had received one dose of streptomycin. C, Six year old negro female who was alert and had a left peripheral facial palsy at the time EEG was taken. Meningeal symptoms began 12 days previously. She had received 3 days of streptomycin. D, Nine and one-half year old ~egro female who developed signs and symptoms of tuberculous meningitis 3 days prior to the tracing. She was irrational but demonstrated no focal neurologie signs. She had received one day of streptomycin treatment. E, Eighteen year old untreated white female who developed meningeal symptoms one day previously. S t i f f neck, drowsiness, and a temperature of 103 ° 1~ were present at this time. F, Thirty-three year old negro female who had a temperature of 103 ° F and was drowsy. Meningeal symptoms began 16 days earlier. She had received no therapy at the time this record was made. G, Thirty-four year old white female who developed meningeal symptoms 5 days prior to this tracing. She was anorexic and complained of severe headache at this time. Streptomycin had been administered for 6 - d a y s . An untreated 45 year old white male with lethargy, disorientation and a stiff neck at the time tracing was made. Meningeal symptoms began 18 days previous. Note that the initial EEGs in children (A, B, C and D) who had received little or no streptomycin are uniformly and diffusely slow. However, those in adults (E, F, G and H ) , taken under similar circumstances show, at best, only a mild amount of delta activity. In children, in the presence of an untreated lymphocytic me/,ingitis, a diffusely slow EEG may be indicative of tuberculosis.
58
R . C . TURRELL, W. SHAW, R. P. SCHMIDT, L. L. LEVY and E. ROSEMAN
(11
9+ I0 On. 12)
Gall A
FIGURE ]Z
21st Oay
30th Ooy
'..b~,,v~ A ,',rVLA--"Z ~
9+10 Gn.(3 }
(I)
34th Day
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~ ' ~ . J ~
Gall 8
IGth Day
23rd Day
3"9
~31
28th Day
11-9 9+ I0 Gn. 14)
9 + 1 0 Gn.
36th Day
(41
29th Doy
EEG S T U D I E S OF T H E E N C E P H A L O P A T H I E S
similar. T h e y i l l u s t r a t e the m a r k e d d i f f e r ences i n the E E G i n c h i l d r e n a n d a d u l t s w i t h a s i m i l a r clinical course. F i g u r e 3 shows the serial electroencepha l o g r a p h i c p i c t u r e i n a child w i t h a p r o l o n g ed v a c i l l a t i n g clinical course t e r m i n a t i n g fat a l l y a f t e r 290 days. The p a t i e n t was a 7 y e a r old n e g r o male who developed s i g n s of m e n i n g i t i s 7 d a y s p r i o r to the first E E G . W i t h i m p r o v e m e n t the E E G became f a s t e r ; w h e n his c o n d i t i o n w o r s e n e d it became slower. F i g u r e 3 also shows the i m p r o v e m e n t seen e a r l y w i t h s t r e p t o m y c i n t h e r a p y . Improvement under streptomycin therapy u s u a l l y o c c u r r e d c l i n i c a l l y a n d electroencepha l o g r a p h i c a l l y b e t w e e n the 7 a n d 14 days. F i g u r e 4 d e m o n s t r a t e s serial E E G c h a n g e s i n a case of a r r e s t e d t u b e r c u l o u s m e n i n g i t i s i n a 31/_, y e a r old white female who was t r e a t ed with i n t r a t h e c a l a n d i n t r a m u s c u l a r strept o m y c i n for 5 m o n t h s . These records dem o n s t r a t e d the g r a d u a l e v o l u t i o n of t u b e r c u l o u s e n c e p h a l o p a t h y f r o m the acute to the a r r e s t e d state. She developed t e m p e r t a n trums, nightmares and behavior disturbances in the y e a r f o l l o w i n g d i s c h a r g e f r o m the hospital. The last E E G (fig. 4 ( 6 ) ) shows m a n y slow spike discharges with a n a m p l i t u d e decrease i n the r i g h t t e m p o r a l area. O t h e r t h a n t e m p e r t a n t r u m s the p a t i e n t is now enj o y i n g good h e a l t h a n d is f u n e t i o n i u ~ well in school.
59
DISCUSSION
O t h e r i n v e s t i g a t o r s have p u b l i s h e d r e p o r t s on the p r o g n o s t i c v a l u e of serial electroe n e e p h a l o g r a p h y i n t u b e r c u l o u s meningiti~. Garsehe a n d Dlugosch (1951) r~.ported on 50 c h i l d r e n with t u b e r c u l o u s m e n i n g i t i s followed with E E G s . O n l y 10 were r(,eorded in the i n i t i a l u l l t r e a t e d state. T h e y c o n c l u d e d t h a t the first E E G is u s u a l l y slou ~ a~ld t h a t the a m o u n t of d e l t a a c t i v i t y in follow-up records c o r r e s p o n d s best with tt~,~, level of consciousness. No E E G eorrelatiol~s could be m a d e w i t h b o d y t e m p e r a t u r e , bl,,od chemistries or c e r e b r o s p i n a l f l u i d fir, dings. I n s u b j e c t s who i m p r o v e d with s t r e p t o m y c i n t h e r a p y , f a v o r a b l e E E G c h a n g e s were n o t e d b e t w e e n the 60th a n d 120th day. A persiste n t l y slow E E G i n d i c a t e d a poor prognosis. Mattei et al. (1951) recorded s(~rial E E G s in 26 p a t i e n t s . None of t h e i r s u b j e c t s were seen early. T h e y p o i n t e d out the p r o g n o s t i c i m p o r t of serial E E G . Debre (1952) n o t e d importan~ E E G alt e r a t i o n s i n 43 out of 77 c h i l d r e n with t u b e r culous m e n i n g i t i s . H e believed the E E G to be of p r o g n o s t i c v a l u e b u t gave o n l y a few details. F r o m the p r e s e n t s t u d y , it would a p p e a r t h a t the E E G when done serially in t u b e r eulous m e n i n g i t i s , is of v a l u e both diagnostically and proguostically.
Fig. 2 The EEG picture of a rapidly fatal case of tuberculous meningitis in a child (A) and an adult (B). Case A. - - M. J. 13 month old white male who developed signs and symptoms of tuberculous meningitis on March 27, 1951. (1) EEG taken 21 days after onset shows diffuse high voltage ~low activity. He had received no streptomycin prior to this tracing. (2) After 8 days of streptomycin intrathecally and intramuscularly there is less delta activity. This paralleled the mild clinical improvement noted. (3) On the 34th day of illness the slow activity is very marked. At this time the patient was decerebrate and semiconscious. (4) On the 36th day of illness there was little change in the diffuse slow activity. Clinically the patient was moribund. He died 24 hours after this tracing was taken. Note the amplitude asymmetry. This is a common finding in the terminal state in children. Case B. -- O. L. C. 33 year old colored female who developed signs and symptoms of tuberculous meningitis on 3-1-51. (1) ]~EG taken on 16th day of illness shows a dysrhythmie record with no definite delta activity. Streptomycin had not been given. (2) On tile 23rd day of illness she was disoriented. Tracing shows diffuse mild slowing. (3) On the 28th (lay she had convulsions and Cheym,-Stokes respiration. EEG shows mild slowing. (4) Two days prior to death, on the 29th day of illness, she was comatose. The tracing shows only a slight amount of delta activity. Note that in adults, even in the terminal phases of their illness, the EEG may show comparatively little slowing. In children, however, persistence of delta activity augurs clinical alterations in the patients which may I?e profound and irreversible.
60
R . C . TURRELL, W. SHAW, R. P. SCHMIDT, L. L. LEVY and E. ROSEMAN
El)
"?th DOy
~
~,~
~ ~ , ~ . (2)
,6th Ooy
(3)
22rid Ooy
8-13
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(5)
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-|
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-~_.,. ~ ....................... )10 iS) 3~13
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(7) "
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-
FIGURE lrn
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141
(e)
70th Ooy
191 3 -13
2eOthOoy
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E E G S T U D I E S OF T H E E N C E P ~ A L O P A T H I E S
Most striking is the observation of the marked difference between the initial EEGs in adults and children. In the latter, the initial E E G in those not treated was invariably a diffusely slow one. This alteration in the E E G is present at all ages in children and is not related to the duration of illness. On the other hand, untreated adults have comparatively little delta activity in their initial tracings. Most investigators agree that the earlier the diagnosis is established and the more rapidly specific energetic therapy is instituted, the better the chance for arresting the disease. The diffuse high voltage slow activity seen in children with untreated tuberculous meningitis therefore, may be of some diagnostic value. In an untreated lymphocytic meningitis in childhood, tuberculous meningitis can be suspected if the E E G is diffusely and markedly slowed, and it can be excluded in children with relatively normal EEGs. Therefore the E E G in children would seem to offer aid in establishing the early diagnosis of tuberculous meningitis and improving the ultimate prognosis of the disease. In adults the initial E E G was of little or no help from the diagnostic standpoint. The E E G would seem to be of aid in prognosis. Alterations in the E E G parallel
61
and not infrequently precede changes in the clinical course. Increased delta activity is usually associated with increased morbidity; conversely, diminution of the delta activity augurs well. This parallelism was more evident in children than adults. By the study of serial electroencephalograms it is sometimes possible to foresee a relapse or to detect an exacerbation of the disease process before it has produced very serious consequences; for example, a sudden increase in electroencephalographic abnormality may raise a suspicion of hydrocephalus or bl¢)ck. Serial studies are particularly useful for following patients in their convalescent phase when they are receiving only intramuscular streptomycin and daily spinal taps have been discontinued. At some time during a favorable course of treated tuberculous meningitis, the question arises as to when ther~py should be stopped. If focal or diffuse slaw activity is still present, even in the face of approaching normal spinal fluid findings, it is probably unwise to discontinue treatm~nt. The large number of seizures noted in this series should be remarked upon The incidence of 82 per cent would seem to indicate the need for anticonvulsant medication in the routine management of tuberculous meningitis.
Fig. 3 A prolonged case of streptomycin-treated tuberculous meningitis ending fatally. E. B. Seven year old colored male who developed signs and symptoms of tuberculous meningitis on May 9, 1950. (1) EEG taken on the 7th day of illness shows diffuse high voltage slow activity. The patient was lethargic, confused and had a left lateral rectus palsy. (2) A f t e r 10 days of intrathecal and intramuscular streptomycin (16th day of illness) he had made considerable clinical improvement The EEG shows much less slow activity. (3) On the 22nd day he was more lethargic and demonstrated bilateral papilledema. The EEG is slower. (4) During the next six weeks he showed gradual clinical improvement. He became alert, took food orally and the right lateral rectus palsy was clearing at the time of this tracing (70th day). Only a moderate amount of slow waves is present. (5) Four months l.qter, on the 195th day of illness, the patient was ssymptomatie, alert, ambulatory and had no focal neurolo~ic signs. He was discharged from the hospital 5 days later after receiving streptomycin for 6 months. The tracing shows a dysrhythmie record but no delta activity. (6) Two months later the patient relapsed. He was vomiting, was very lethargic and had a left lower facial weakness. At this time (245th day) the E E G is slower than the previous one. (7) By the 277th day of illness he had become moribund. The first dose of intrathecal P. P. D. was administered one day previously. (8) Three days later, after he had received a total of two doses of intratheeal P. P. D., the patient had improved to ~ responsive but still semiconscious state. I t was felt that intratheeal P. P. D. may have contributed to his clinical improvement. The E E G shows considerable decrease in slow activity. (9) Following this brief clinical respite the patient worsened rapidly and died on the 290th day of illness. The EEG taken one day prior to death shows diffuse high voltage slow activity. At post mortem a subarachnoid block in the cervical area was demonstrated. This series" shows the vacillations of the E E G corresponding to the fluctuating clinical status.
62
1~. C. TURRELL, W. SHAW, R. P. SCHMIDT, L. L. LEVY and E. ROSEMAN
(I)
21st Doy
FIGURE
~'
(4)
112th Doy
7.
7
II
8 9+lOGn
.
.
""
- -
I-,~,,~
I
91"lOGn.
.
3
e 9+10 Gn. ~'t'l(~ ~ n (3)
52nd Ooy
(61 28 months offer onset
Fig. 4 The evolution of the EEG in an arrested case of tuberculous meningitis. J. B. A 31/~ year old white female who developed signs and symptoms of meningitis on April 9, 1945. (1) Taken on the 21st day of illness after 10 days of streptomycin therapy. The patient had already begun to show some clinical improvement. She was still lethargic, but had no focal neurological signs. The tracing shows moderste diffuse delta activity. (2) On the 35th day of illness she was more alert but had developed measles. In spite of this the tracing shows lessening of the slow activity. (3) She was alert, ambulatory and afebrile by the 52nd day. There is considerable resolution of the slow activity. (4) Two months later she was completely asymptomatic. The record on the l l 2 t h day shows only an occasional slow spike discharge. She was discharged from the hospital on the 160th day of illness with normal spinal fluid and asymptomatic. (5) On the 204th day of illness the patient was doing well at home. The EEG is essentially normal. For the next 21 months she continued to do well at home with the exception of occasional temper tantrums and nightmares. (6) EEG taken 28 months after onset of tuberculous meningitis shows a very dysrhythmie record. She was now placed on anticonvulsant medication. Her behavior pattern has improved and she no longer has nightmares. She is a " s t r a i g h t A " student in school. The parents state at the time of this writing (41/~ years) that the child is asymptomatic.
EEG STUDIES OF THE ENCEPHALOPATHIES
SUMMARY Serial clinical and electroeneephalographie correlations were made in 57 proven cases of tuberculous meningitis. Thirty-six children and 21 adults were included. The number of E E G s per patient varied from one to 33 and included observation periods from 3 days to 4 years. The records of adults and children differ markedly. I n untreated adults the initial E E G is at most only midly slow. Terminally, the adult record shows only moderate slowing. Untreated children show very slow E E G s initially. Diagnostically, the E E G would seem to be of value in children. I n an untreated lymphotic meningitis, tuberculous meningitis can be suspected or excluded on the basis of the initial E E G , since the record is invariably v e r y slow if tuberculosis is present. Prognostically, E E G changes usually parallel or precede the clinical alterations. W i t h improvement in the p a t i e n t ' s condition the E E G becomes faster. Serial records enable one to suspect the development of seizures,
63
hydrocephalus or relapse. The prognosis for recovery is poor in a n y patient who shows a very slow record with an amplitude reduction on one side for a two week period. The large number of patients with seizure discharges in the E E G seems to correlate with the high incidence (over 80 per cent) of clinical seizures observed in the present series. REFERENCES DEBRE, R. The prognosis of tuberculous meningitis. Aqner. Rev. Tuberc., 1952, 65: 168-18,). GARSCHE, R. und DLU{]OSCH, G. ~ber Veriinderun-
geu der Hirnstromkurve bei Meningitis tuberculosa vor und unter Streptomycinbehandiung im Kindesalter. Z. Kinderhk., 1951, 69: 387411. MATTEI~ CH., GASTAUT~ H., PAYAN~ H., BALOZET2
P. et CHOUX,J. Valeur pronostique ,te l'~leetroene~phalogramme au tours du traitement par streptomycine chez l'adulte des meningites tuberculeuses et des miliaires. Presse lfed., 1951, 59 : 1057-1060. To date, nine patients have received isonicotinic acid derivatives either alone or in combination with streptomycin in the therapy of tuberculous meningitis. Preliminary studies suggest a more rapid favorable response clinically which correlates with the more rapid resolution of delta activity in the EEG.
Refere~oe: TURRELL, R. C., SHAW, W., SCHMII~, R. P., LEVY, L. L. and ROSEMAN, E. Eleetroeneephalographic studies of the eneeph~lopathies: If. Serial studies in tuberculous meningitis. E E a C ~ . /~reurophy~o|., ltM, 5: 53-63.
STUDIES OF T H E
ENCEPHALOPATHIES : II. SERIAL STUDIES IN TUBERCULOUS MENINGITIS WILMA SHAW, R.N., RICHARD P. SCHMIDT,M.D., LEwis L. LEvy, M.D. a n d EPHRAIM ROSEMAN, M.D. Sections of Neurology and Electroencephalography, University of Louisville, School of Medicine, and the Louisville General Hospital, Louisville, Ky.
RICHARD C.
TURRELL,M.D.,
This report covers a 41/~ year period during which serial electroencephalographic and clinical correlations were made in 57 proven eases of tuberculous meningitis. The purpose of this paper is to point out the value of serial electroencephalograms in the diagnosis and prognosis of this disease. METHODS Electroencephalograms were performed as soon as possible after admission to the hospital on patients suspected of having tuberculous meningitis. Thereafter tracings were taken at weekly intervals or more frequently if clinical change occurred. In each instance close clinical supervision and electroencephalographic correlation was made by one of the authors. EEGs were made on a Grass eight-channel ink writing oscillograph. A minimum of 13, 27 gauge, needle electrodes were inserted into the scalp and ear lobes, using bipolar as well as monopolar leads (with an average reference or one on both ears or on the cortex). MATERIAL Ages: There were 36 children and 21 adults. The ages ranged from 4 months to 74 years. Thirty-two patients were less than 7 years old. Seven were between 7 and 20 years; 18 were in the 21 to 74 year range. Sex and races: Of the females. 18 were white and 8 were negro. Twenty males were white and 11 were negro. Diagnostic criteria: All cases had a predominantly lymphocytic meningitis with a decreased cerebro-spinal fluid (CSF) sugar and chlorides. In 48 the tubercle bacillus was isolated from the CSF by direct smear,
culture, guinea pig inoculation or were found in the tissues at post mortem examination. In the remaining 9 the diagnosis was suspected by at least 2 characteristic CSF examinations plus evidence of extra central nervous system (CNS) tuberculosis. The characteristic spinal fluid contained up to 500 cells (predominantly lymphocytes) per mm s, sugar less than 30 rag. per cent, chlorides less than 600 mg. per cent and an elevated total protein. Tuberculosis outside the CNS: Only 7 subjects showed no evidence of extra-CNS tuberculosis. Six of these were children and one was an adolescent. The remainder had pulmonary, miliary, bone or other visceral evidence of the disease. Duration of life: The duration of life in those that died ranged from 3 to 360 days (av. 88 days). Eleven patients are living at present (19 per cent survival rate}. Only one adult in the series is alive. He is under treatment and doing well after 279 days of streptomycin therapy. The remaining 10 are children who have lived from 200 to 1640 days. They are all clinically well. Three are still receiving streptomycin. Three others have been followed 4 years or longer. Complications: As noted in table I there was a high incidence of neurological complications. The most frequent were hemiparesis and subarachnoid block with secondary hydrocephalus. Seizures: Forty-seven patients (82 per cent) had seizures at some time during their illness. The majority of these were of a convulsive nature. A few developed ps:...,homotor seizures.
[sa ]
R. (‘. TI’RKEI,L,
.54
_
Casr
1 2 3 4 .i 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 2.7 24 2.5 26 27
28 29 3n 31 30 i.7 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57
rntirnt T-__-JR BT HV GS R(‘” z: DT .TR MJ BW 4 .PR (Y’ TVW* J,E .TF TIT, RB= 1,Tl 1,M VB .TG MG -+ Vu311%. JR MR TP z PS” LW EB DS R,K T,S RG GM MH FS GM DA1 JJ WH EM LG .JS* OC PO’ DT JG’ TR Tsc”” MM RW JL
W. SHAW.
Age
in years
1 1
4/l!? 5/12 i/12 8112 S/l” 11/l” 11/12 11/12 l/12
1 l/12 1 3/12
1 5/12 1 6/12 1 10/12 1 IO/l2 2 2 2 2 2 6/12 2 6/l” 2 (1/l? 3 3 3 c/12 4 5 6 6 6 (i 1: 11 14 I6 18 10 OR 24 24 24 26 28 31 31 33 33 34 36 39 44 45 45 49 74
R. P. SCHMIDT,
L. I,. LEVY
awl E. ROSEMAN
Sex avd Race (1)
HOW prorcx (2)
Extra Cns Tbc (3
CM WF C’M WM CM WM WM WM WM WM WF WF WF t:;M WF WM war WF CF WM WF x.31 WF WF WM WF WM wxr WF CF W’bl WM CM (‘F WM WF CF WF WF CM WF CF CM CM WF CF WM CF WM WF CM WM WF WM CM (‘F CM
S;C F C S:G G:P F s G :t: s r C F F P S;C S C G C S;C;P F F G;S s F S:C;G s S s s F G P 8:P S;P S:(’ S P;G S C P s ;c P C;G
P P 1’ P M;P M P
&;P C S P (‘:S:G P S:P P S F S S:P
None
P P P I’ P P P P P M M;B P P So11e 3r .-P 3f;B P 31 nr Sour P EO,, Sane SOW hL
I&/s of Life (4) e____ 330 I32
18 i8 35 “I) _I Ii0 16 209 L 37 (ii 2.52 106
15 IliT,
21OL 47 4.5 11 120 1490 IA 206 35 31 640 L 1511 L 10 210 I, 151 61 142 1640 I, 290 34
P
Ii5
NOlW
200
P
847 L 58 25 209 32 96 19 20 iR 10 256 26 163 51 I16 3 28 “79 1, 1FUl A.5 19
Al
G nr If 31
M;R P PC. P s P 11 P 31 P P
-
-
p’ M :E
* IM Streptnmyein ody. ** Untreated. (1) C-Negro; W-Crucasian. (2) S-Smear; C-Culture; P-Post Mortem : G-Guinea Pig: F-Presumptive. (3) M-Miliary ; P-Pulmounry ; B-Bone ; 8.Selpingitin; E-Epididymitis; Pe-Peritonitis: R-Renal. (4) Computed ZIR of 1 July JO:
I,
E E G S T U D I E S OF T H E E N C E P H A L O P A T H I E S
55
TABLE I A S U M M A R Y O F 57 C A S E S O F T U B E R C U L O U S M E N I N G I T I S "
Seizures X X X X X X X X X X X X X X X X X X O X O X X X O X X O X X X X X X X X X X X X O X 0 0 X O X X O X X O X X X X X
Number of E g g ' s 38 3 4 3 5 1 10 2 11 5 5 II 3 1 16 4 2 5 1 2 14 7 5 1 6 15 2 17 9 8 2 31 31 4 20 17 34 7 (; 4 2 19 1 3 9 2 3 5 3 7 6 5 3 28 14 4 4
Days ill prior to 12 26 4 15 5 21 14 7 5 2I 17 23 25 6 8 16 5 7 2 62 14 31 9 °7 10 21 7 11 15 12 90 49 7 3 8 15 7 22 12 64 30 30 14 12 6 5 17 12 29 6 20 1 7 12 39 14 4
Initial EEG Days R x prior to 0 16 1 4 0 4 4 0 0 0 2 1 25 0 7 10 1 o 3 6O 0 ]~ o 16 .5 TO 0 4 0 .q 80 42 1 1 0 1 2 0 0 56 86 0 o o 0 0 0 0 18 6 11 0 0 0 14 0 0
Average frequency 3 2.5 1 2.5 2 .5 2.5 2 2.5 2 2 1 1.5 3.5 4 2 1.5 2.5 1 3.5 1.5 .5 4.5 1 2.5 2.5 l 2 1.5 1 1 5 1.5 1.5 2..5 1.5 5 8 3 9 7 2 9 2.5 6 7 7 9.5 7 9 10 7 7 7 2.5 15 3.5
R~marlcs (5) Subd. llygrom't; hydro. Hydro. L. L. L. R.
Hemip. Hemip. Hemip. Hemip.
L. H e m i p . ; Subaraeh. block. Men. folh)wed Rx for exl-a C N S tbe. Decerebrate; hydro. Deeerebrate R. Hemip. Deaf Decerebrate ; hydro. R. Hemip. R. Hemip. Hydro. R. H e m i p . ; Improved. Hydro. Measles prior to men. L. Hemip. Well WeU Measles prior to men. ; R Hcmip. Cerebral m u m p s d u r i n g illness ; Des: Subarach. block ; L e f t Ilemip. Hydra. Decerebrate Cerebral m u m p s d u r i n g i Ihmss. Subarach. block Measles prior to men. Blind ; quadriplegia S M N eneeph.; d e a f ; L. Hemip. Quadriparetic ; now wel! Men. 2 days post p a r t u m P a r a p l e g i c ; subaraeh. Idoek Men. developed under S M N Rx Hydro.; L. Ile/nip. R. Hemip.
Tubereuloma R. Cerebellum Men. followed Rx for ext ra-CNS tbe. L. Hemip. R. Hemip. Men. post p a r t u m L. Hemip. Men. followed Rx for ext ra-CNS tl)e. R. Hemip. Subarach. block; now a s y m p t o m a t i c Men. followed ]~x f o r extra-CNS the. Tubereuloma R. cerebellum
L-lAving. (5) S u b d . - S u d u r a l ; H y d r o . - H y d r o e e p h a l u s ; S u b a r a c h . - S u b a r a c h n o i d ; Men.-Meningitis: S M N - S t r e p t o m y c i n ; E n c e p h . - E n e e p h a l o p a t h y ; Hemip.-Hemiparesis.
56
R. C. TURRELL,
Case A
Case
C
Case
D
W. SHAW,
R. P. SCHMIDT,
FIGURE I
L. L. LEVY
and E. ROSEMAN
Case E
Case G
EEG STUDIES OF THE ENCEPHALOPATHIES Electroencephalograms: A total of 502 E E G were performed. The average number p e r patient was 8 and ranged from one to 33. Improvement, if it occurred, was noted both clinically and electroencephalographically between the 7th and 14th day. Twentysix patients had no treatment prior to their initial E E G . An additional 17 patients had been treated for 7 days or less prior to their first record. This made a total of 43 on whom initial E E G s were performed before t h e r a p y could alter their clinical or electroencephalographic course. The remaining 14 patients had been treated for variable periods of time prior to their first E E G . Three of the latter developed meningitis during or following streptomycin t h e r a p y for extra-CNS tuberculosis. The initial E E G s of all patients were classified according to their average dominant frequency. I n children this r a n g e d from 0.5 to 4.5 c/see, with an average of 1.5. F o r adults this was much faster and a v e r a g e d 6.5 c/see. RESULTS The initial E E G s in adults and children differed markedly. In adults not treated with streptomycin the first E E G was only mildly slow. In children, however, the original record was invariably diffusely slow. This disseminated delta activity was seen in
57
children of all ages and was present irrespective of the length of illness prior to the first record. F i g u r e 1 is a compariso~ of the initial E E G s in 4 adults and 4 children with tuberculous meningitis. The adults had been ill a comparable or longer peri()d of time than the children. Electroencephalographic changes paralleled and f r e q u e n t l y preceded the clinical changes. Improvement in the clinical status was reflected in the E E G by a decrease in slow activity; clinical worsening by an increase. In adults the serial E E G changes were much less marked than in children. F i g u r e 2 contrasts the electroencephalo: graphic course of an adult and a child with tuberculous meningitis. Both received i n t r a t h e c a l and intramuscular streptomycin after recording the initial EEGs. In each instance the duration of life was short. Ca.~e A is that of a 13 months old white male who lived 37 days after the onset of tuberc~llous meningitis. Serial E E G s show progressive increase of delta activity until death. H i s clinical course was one of increasing lack o f awareness progressing to coma ~nd death. Case B is a 33 year old colored female who lived 31 days. Serial tracings show only a mild degree of slowing even just prior to death. Length of life, level of consciousness and t h e r a p y in these two cases were v e r y
Fig. 1 The initial EEG in adults and children with tuberculous meningitis. A, Seven month old negro male who developed meningeal symptoms 4 days previously. He was irritable, had a stiff neck" and a right lower facial weakness. He had received one dose of streptomycin at this time. B, Two year old white male who had a stiff neck, lethargy and no focal neurological signs at the time of this tracing. Meningeal symptoms began 5 days earlier. He had received one dose of streptomycin. C, Six year old negro female who was alert and had a left peripheral facial palsy at the time EEG was taken. Meningeal symptoms began 12 days previously. She had received 3 days of streptomycin. D, Nine and one-half year old ~egro female who developed signs and symptoms of tuberculous meningitis 3 days prior to the tracing. She was irrational but demonstrated no focal neurologie signs. She had received one day of streptomycin treatment. E, Eighteen year old untreated white female who developed meningeal symptoms one day previously. S t i f f neck, drowsiness, and a temperature of 103 ° 1~ were present at this time. F, Thirty-three year old negro female who had a temperature of 103 ° F and was drowsy. Meningeal symptoms began 16 days earlier. She had received no therapy at the time this record was made. G, Thirty-four year old white female who developed meningeal symptoms 5 days prior to this tracing. She was anorexic and complained of severe headache at this time. Streptomycin had been administered for 6 - d a y s . An untreated 45 year old white male with lethargy, disorientation and a stiff neck at the time tracing was made. Meningeal symptoms began 18 days previous. Note that the initial EEGs in children (A, B, C and D) who had received little or no streptomycin are uniformly and diffusely slow. However, those in adults (E, F, G and H ) , taken under similar circumstances show, at best, only a mild amount of delta activity. In children, in the presence of an untreated lymphocytic me/,ingitis, a diffusely slow EEG may be indicative of tuberculosis.
58
R . C . TURRELL, W. SHAW, R. P. SCHMIDT, L. L. LEVY and E. ROSEMAN
(11
9+ I0 On. 12)
Gall A
FIGURE ]Z
21st Oay
30th Ooy
'..b~,,v~ A ,',rVLA--"Z ~
9+10 Gn.(3 }
(I)
34th Day
~113--412)10(2)
~ ' ~ . J ~
Gall 8
IGth Day
23rd Day
3"9
~31
28th Day
11-9 9+ I0 Gn. 14)
9 + 1 0 Gn.
36th Day
(41
29th Doy
EEG S T U D I E S OF T H E E N C E P H A L O P A T H I E S
similar. T h e y i l l u s t r a t e the m a r k e d d i f f e r ences i n the E E G i n c h i l d r e n a n d a d u l t s w i t h a s i m i l a r clinical course. F i g u r e 3 shows the serial electroencepha l o g r a p h i c p i c t u r e i n a child w i t h a p r o l o n g ed v a c i l l a t i n g clinical course t e r m i n a t i n g fat a l l y a f t e r 290 days. The p a t i e n t was a 7 y e a r old n e g r o male who developed s i g n s of m e n i n g i t i s 7 d a y s p r i o r to the first E E G . W i t h i m p r o v e m e n t the E E G became f a s t e r ; w h e n his c o n d i t i o n w o r s e n e d it became slower. F i g u r e 3 also shows the i m p r o v e m e n t seen e a r l y w i t h s t r e p t o m y c i n t h e r a p y . Improvement under streptomycin therapy u s u a l l y o c c u r r e d c l i n i c a l l y a n d electroencepha l o g r a p h i c a l l y b e t w e e n the 7 a n d 14 days. F i g u r e 4 d e m o n s t r a t e s serial E E G c h a n g e s i n a case of a r r e s t e d t u b e r c u l o u s m e n i n g i t i s i n a 31/_, y e a r old white female who was t r e a t ed with i n t r a t h e c a l a n d i n t r a m u s c u l a r strept o m y c i n for 5 m o n t h s . These records dem o n s t r a t e d the g r a d u a l e v o l u t i o n of t u b e r c u l o u s e n c e p h a l o p a t h y f r o m the acute to the a r r e s t e d state. She developed t e m p e r t a n trums, nightmares and behavior disturbances in the y e a r f o l l o w i n g d i s c h a r g e f r o m the hospital. The last E E G (fig. 4 ( 6 ) ) shows m a n y slow spike discharges with a n a m p l i t u d e decrease i n the r i g h t t e m p o r a l area. O t h e r t h a n t e m p e r t a n t r u m s the p a t i e n t is now enj o y i n g good h e a l t h a n d is f u n e t i o n i u ~ well in school.
59
DISCUSSION
O t h e r i n v e s t i g a t o r s have p u b l i s h e d r e p o r t s on the p r o g n o s t i c v a l u e of serial electroe n e e p h a l o g r a p h y i n t u b e r c u l o u s meningiti~. Garsehe a n d Dlugosch (1951) r~.ported on 50 c h i l d r e n with t u b e r c u l o u s m e n i n g i t i s followed with E E G s . O n l y 10 were r(,eorded in the i n i t i a l u l l t r e a t e d state. T h e y c o n c l u d e d t h a t the first E E G is u s u a l l y slou ~ a~ld t h a t the a m o u n t of d e l t a a c t i v i t y in follow-up records c o r r e s p o n d s best with tt~,~, level of consciousness. No E E G eorrelatiol~s could be m a d e w i t h b o d y t e m p e r a t u r e , bl,,od chemistries or c e r e b r o s p i n a l f l u i d fir, dings. I n s u b j e c t s who i m p r o v e d with s t r e p t o m y c i n t h e r a p y , f a v o r a b l e E E G c h a n g e s were n o t e d b e t w e e n the 60th a n d 120th day. A persiste n t l y slow E E G i n d i c a t e d a poor prognosis. Mattei et al. (1951) recorded s(~rial E E G s in 26 p a t i e n t s . None of t h e i r s u b j e c t s were seen early. T h e y p o i n t e d out the p r o g n o s t i c i m p o r t of serial E E G . Debre (1952) n o t e d importan~ E E G alt e r a t i o n s i n 43 out of 77 c h i l d r e n with t u b e r culous m e n i n g i t i s . H e believed the E E G to be of p r o g n o s t i c v a l u e b u t gave o n l y a few details. F r o m the p r e s e n t s t u d y , it would a p p e a r t h a t the E E G when done serially in t u b e r eulous m e n i n g i t i s , is of v a l u e both diagnostically and proguostically.
Fig. 2 The EEG picture of a rapidly fatal case of tuberculous meningitis in a child (A) and an adult (B). Case A. - - M. J. 13 month old white male who developed signs and symptoms of tuberculous meningitis on March 27, 1951. (1) EEG taken 21 days after onset shows diffuse high voltage ~low activity. He had received no streptomycin prior to this tracing. (2) After 8 days of streptomycin intrathecally and intramuscularly there is less delta activity. This paralleled the mild clinical improvement noted. (3) On the 34th day of illness the slow activity is very marked. At this time the patient was decerebrate and semiconscious. (4) On the 36th day of illness there was little change in the diffuse slow activity. Clinically the patient was moribund. He died 24 hours after this tracing was taken. Note the amplitude asymmetry. This is a common finding in the terminal state in children. Case B. -- O. L. C. 33 year old colored female who developed signs and symptoms of tuberculous meningitis on 3-1-51. (1) ]~EG taken on 16th day of illness shows a dysrhythmie record with no definite delta activity. Streptomycin had not been given. (2) On tile 23rd day of illness she was disoriented. Tracing shows diffuse mild slowing. (3) On the 28th (lay she had convulsions and Cheym,-Stokes respiration. EEG shows mild slowing. (4) Two days prior to death, on the 29th day of illness, she was comatose. The tracing shows only a slight amount of delta activity. Note that in adults, even in the terminal phases of their illness, the EEG may show comparatively little slowing. In children, however, persistence of delta activity augurs clinical alterations in the patients which may I?e profound and irreversible.
60
R . C . TURRELL, W. SHAW, R. P. SCHMIDT, L. L. LEVY and E. ROSEMAN
El)
"?th DOy
~
~,~
~ ~ , ~ . (2)
,6th Ooy
(3)
22rid Ooy
8-13
~_yy~
(5)
195th Doy
-|
~_ 91,II 3 - - 4 ~
-~_.,. ~ ....................... )10 iS) 3~13
245th Day
(7) "
277thOoy
I-9
3-9
-
FIGURE lrn
~~,/,~,~,
141
(e)
70th Ooy
191 3 -13
2eOthOoy
289th Doy
E E G S T U D I E S OF T H E E N C E P ~ A L O P A T H I E S
Most striking is the observation of the marked difference between the initial EEGs in adults and children. In the latter, the initial E E G in those not treated was invariably a diffusely slow one. This alteration in the E E G is present at all ages in children and is not related to the duration of illness. On the other hand, untreated adults have comparatively little delta activity in their initial tracings. Most investigators agree that the earlier the diagnosis is established and the more rapidly specific energetic therapy is instituted, the better the chance for arresting the disease. The diffuse high voltage slow activity seen in children with untreated tuberculous meningitis therefore, may be of some diagnostic value. In an untreated lymphocytic meningitis in childhood, tuberculous meningitis can be suspected if the E E G is diffusely and markedly slowed, and it can be excluded in children with relatively normal EEGs. Therefore the E E G in children would seem to offer aid in establishing the early diagnosis of tuberculous meningitis and improving the ultimate prognosis of the disease. In adults the initial E E G was of little or no help from the diagnostic standpoint. The E E G would seem to be of aid in prognosis. Alterations in the E E G parallel
61
and not infrequently precede changes in the clinical course. Increased delta activity is usually associated with increased morbidity; conversely, diminution of the delta activity augurs well. This parallelism was more evident in children than adults. By the study of serial electroencephalograms it is sometimes possible to foresee a relapse or to detect an exacerbation of the disease process before it has produced very serious consequences; for example, a sudden increase in electroencephalographic abnormality may raise a suspicion of hydrocephalus or bl¢)ck. Serial studies are particularly useful for following patients in their convalescent phase when they are receiving only intramuscular streptomycin and daily spinal taps have been discontinued. At some time during a favorable course of treated tuberculous meningitis, the question arises as to when ther~py should be stopped. If focal or diffuse slaw activity is still present, even in the face of approaching normal spinal fluid findings, it is probably unwise to discontinue treatm~nt. The large number of seizures noted in this series should be remarked upon The incidence of 82 per cent would seem to indicate the need for anticonvulsant medication in the routine management of tuberculous meningitis.
Fig. 3 A prolonged case of streptomycin-treated tuberculous meningitis ending fatally. E. B. Seven year old colored male who developed signs and symptoms of tuberculous meningitis on May 9, 1950. (1) EEG taken on the 7th day of illness shows diffuse high voltage slow activity. The patient was lethargic, confused and had a left lateral rectus palsy. (2) A f t e r 10 days of intrathecal and intramuscular streptomycin (16th day of illness) he had made considerable clinical improvement The EEG shows much less slow activity. (3) On the 22nd day he was more lethargic and demonstrated bilateral papilledema. The EEG is slower. (4) During the next six weeks he showed gradual clinical improvement. He became alert, took food orally and the right lateral rectus palsy was clearing at the time of this tracing (70th day). Only a moderate amount of slow waves is present. (5) Four months l.qter, on the 195th day of illness, the patient was ssymptomatie, alert, ambulatory and had no focal neurolo~ic signs. He was discharged from the hospital 5 days later after receiving streptomycin for 6 months. The tracing shows a dysrhythmie record but no delta activity. (6) Two months later the patient relapsed. He was vomiting, was very lethargic and had a left lower facial weakness. At this time (245th day) the E E G is slower than the previous one. (7) By the 277th day of illness he had become moribund. The first dose of intrathecal P. P. D. was administered one day previously. (8) Three days later, after he had received a total of two doses of intratheeal P. P. D., the patient had improved to ~ responsive but still semiconscious state. I t was felt that intratheeal P. P. D. may have contributed to his clinical improvement. The E E G shows considerable decrease in slow activity. (9) Following this brief clinical respite the patient worsened rapidly and died on the 290th day of illness. The EEG taken one day prior to death shows diffuse high voltage slow activity. At post mortem a subarachnoid block in the cervical area was demonstrated. This series" shows the vacillations of the E E G corresponding to the fluctuating clinical status.
62
1~. C. TURRELL, W. SHAW, R. P. SCHMIDT, L. L. LEVY and E. ROSEMAN
(I)
21st Doy
FIGURE
~'
(4)
112th Doy
7.
7
II
8 9+lOGn
.
.
""
- -
I-,~,,~
I
91"lOGn.
.
3
e 9+10 Gn. ~'t'l(~ ~ n (3)
52nd Ooy
(61 28 months offer onset
Fig. 4 The evolution of the EEG in an arrested case of tuberculous meningitis. J. B. A 31/~ year old white female who developed signs and symptoms of meningitis on April 9, 1945. (1) Taken on the 21st day of illness after 10 days of streptomycin therapy. The patient had already begun to show some clinical improvement. She was still lethargic, but had no focal neurological signs. The tracing shows moderste diffuse delta activity. (2) On the 35th day of illness she was more alert but had developed measles. In spite of this the tracing shows lessening of the slow activity. (3) She was alert, ambulatory and afebrile by the 52nd day. There is considerable resolution of the slow activity. (4) Two months later she was completely asymptomatic. The record on the l l 2 t h day shows only an occasional slow spike discharge. She was discharged from the hospital on the 160th day of illness with normal spinal fluid and asymptomatic. (5) On the 204th day of illness the patient was doing well at home. The EEG is essentially normal. For the next 21 months she continued to do well at home with the exception of occasional temper tantrums and nightmares. (6) EEG taken 28 months after onset of tuberculous meningitis shows a very dysrhythmie record. She was now placed on anticonvulsant medication. Her behavior pattern has improved and she no longer has nightmares. She is a " s t r a i g h t A " student in school. The parents state at the time of this writing (41/~ years) that the child is asymptomatic.
EEG STUDIES OF THE ENCEPHALOPATHIES
SUMMARY Serial clinical and electroeneephalographie correlations were made in 57 proven cases of tuberculous meningitis. Thirty-six children and 21 adults were included. The number of E E G s per patient varied from one to 33 and included observation periods from 3 days to 4 years. The records of adults and children differ markedly. I n untreated adults the initial E E G is at most only midly slow. Terminally, the adult record shows only moderate slowing. Untreated children show very slow E E G s initially. Diagnostically, the E E G would seem to be of value in children. I n an untreated lymphotic meningitis, tuberculous meningitis can be suspected or excluded on the basis of the initial E E G , since the record is invariably v e r y slow if tuberculosis is present. Prognostically, E E G changes usually parallel or precede the clinical alterations. W i t h improvement in the p a t i e n t ' s condition the E E G becomes faster. Serial records enable one to suspect the development of seizures,
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hydrocephalus or relapse. The prognosis for recovery is poor in a n y patient who shows a very slow record with an amplitude reduction on one side for a two week period. The large number of patients with seizure discharges in the E E G seems to correlate with the high incidence (over 80 per cent) of clinical seizures observed in the present series. REFERENCES DEBRE, R. The prognosis of tuberculous meningitis. Aqner. Rev. Tuberc., 1952, 65: 168-18,). GARSCHE, R. und DLU{]OSCH, G. ~ber Veriinderun-
geu der Hirnstromkurve bei Meningitis tuberculosa vor und unter Streptomycinbehandiung im Kindesalter. Z. Kinderhk., 1951, 69: 387411. MATTEI~ CH., GASTAUT~ H., PAYAN~ H., BALOZET2
P. et CHOUX,J. Valeur pronostique ,te l'~leetroene~phalogramme au tours du traitement par streptomycine chez l'adulte des meningites tuberculeuses et des miliaires. Presse lfed., 1951, 59 : 1057-1060. To date, nine patients have received isonicotinic acid derivatives either alone or in combination with streptomycin in the therapy of tuberculous meningitis. Preliminary studies suggest a more rapid favorable response clinically which correlates with the more rapid resolution of delta activity in the EEG.
Refere~oe: TURRELL, R. C., SHAW, W., SCHMII~, R. P., LEVY, L. L. and ROSEMAN, E. Eleetroeneephalographic studies of the eneeph~lopathies: If. Serial studies in tuberculous meningitis. E E a C ~ . /~reurophy~o|., ltM, 5: 53-63.